Project Summary ? Project 1 Recent public health emergencies, most notably the 2014-2016 Ebola epidemic, have exposed the vulnerabilities in West African health systems and the urgent need for improved global surveillance of infectious disease threats. Despite the burden of infectious disease in this region, the spectrum of circulating microbes, especially viruses, in West Africa is poorly understood. This owes, in part, to the lack of diagnostic capacity to detect known pathogens in many areas, and the nonspecific symptoms caused by many of these microbes, making it difficult to clinically determine the cause of infection. In this context, genomic approaches, including next-generation sequencing, have recently emerged as powerful tools for pathogen detection and discovery, as well as enabling valuable insight into the origins, transmission and biological properties of these pathogens. In this Project, we propose to use cutting edge next-generation sequencing capacity established at the three West African Collaborative Centers to identify known and novel viruses in patients with a fever and healthy controls. We will use computational approaches to assemble full viral genomes and understand the evolutionary dynamics and population genetics of the most important viral threats identified through metagenomic sequencing. Lastly, we will implement novel tools to enhance the efficiency and sensitivity of pathogen sequencing. This project will establish a framework for the sustainable application of powerful sequencing technologies in public health contexts and identify the most pressing viral threats in this region, informing the development of relevant diagnostic tests in Project 2. Furthermore, working across three West African countries, the sequencing efforts of our collaborative center will yield broad insights into the virome across a wide geographic region and allow for the sharing of approaches to enhance biosurveillance across West Africa. Not only will this continue to advance the genomics of infectious disease in West Africa, it will provide immediate, actionable insights to protect local communities and prevent future outbreaks.